The present invention relates generally to an electrode for sensing and/or determining constituents of blood, and more particularly to such an electrode which provides a stable and rugged detection mechanism adapted to determine glucose levels in blood either in-vivo or in-vitro applications. The electrode consists essentially of a silanized iridium oxide substrate having a glucose oxidase film covalently bonded thereto. A protective overcoating layer or film, permeable to glucose and oxygen is utilized as well, the overcoat film protecting the surface of the covalently bonded oxidase film from direct contact with blood, while having good transport properties for the glucose and oxygen constituents of the blood.
The determination of glucose levels in blood is useful in a variety of applications. One particular application is for use by diabetics in combination with an implantable insulin infusion pump system. The use of implantable insulin pumps is frequently indicated for patients, particularly those diabetics whose conditions are best treated or stabilized by the use of implantable insulin infusion pumps. Glucose sensors are useful in combination with such pumps, since these sensors may be used to determine glucose levels and provide information useful to the system to monitor the administration of insulin in response to actual and/or anticipated changes in blood glucose levels. For example, glucose levels are known to change in response to food and beverage intake, as well as to normal metabolic function. While certain diabetics are able to maintain proper glucose-insulin levels with conventional insulin injection or other insulin administration techniques, some individuals experience unusual problems giving rise to the need for a substantially constant glucose monitoring system to maintain an appropriate glucose-insulin balance in their bodies. The electrode of the present invention provides a means for determining the immediate level of glucose in the blood, with the determination being useful in controlling the glucose level at a specific future or anticipated point in time. In this fashion, glucose levels may be controllably adjusted or otherwise implemented into the anticipated normal activity of the individual whose system is being monitored. Consideration is given to time lags which are inherent in all bodily functions, particularly the metabolic processes, thereby providing a means to achieve a proper insulin-glucose balance on an extended time basis. Through use of the sensor of the present invention, glucose and/or insulin levels may be maintained in proper balance and at desired and appropriate levels, by means of timely infusion of appropriate amounts of insulin to the patient's system.
Glucose levels in the bloodstream of a patient vary on a time basis and are normally dependent upon the physical activity of the individual, his food, beverage and sugar intake, his metabolic rate, along with other factors. Accordingly, changes in the insulin-glucose balance occur in direct response to these time dependent variables. Certain implantable insulin infusion pumps are capable of operation at variable and/or programmable delivery rate, with these rates varying in response to increases and decreases in the sensed as well as the desired glucose level. Stated another way, variable rate infusion pumps deliver insulin at a rate determined in part by the immediate glucose level in the blood, and a glucose sensor is utilized to provide information in the form of a signal indicative of the immediate glucose level in the patient's system. Other factors or information useful for the operation of variable rate infusion pumps include dietary and physical activity with both immediate past activity and anticipated activity being considered pertinent. A properly programmed infusion pump will utilize such information and more in order to perform its function and assist the patient in maintaining a proper insulin balance in his system over an extended period of time.
Glucose, as a compound, is difficult to determine on a direct basis electrochemically, since its properties lead to relatively poor behavior during oxidation and/or reduction activity. Furthermore, glucose levels in blood are difficult to determine inasmuch as most mechanisms for sensing and/or determining glucose levels are affected by the presence of other constituents or compounds normally found in blood. For these reasons, it has been found desirable to utilize various enzymes and/or other protein materials which provide specific reactions with glucose and yield readings and/or by-products which are capable of analyses quantitatively. Accordingly, a number of procedures are available for quantitative determination of glucose, including quantitative determination of glucose in blood utilizing enzymes. However, these procedures are tyically not adaptable for in-vivo applications, and for the most part find difficulty in being adapted for even simple in-vitro determinations.
More recently, chemically modified electrodes have been applied to certain electrochemical sensing operations. In this connection, enzymes or other reagent proteins may be covalently attached to the surface of an electrode, and thereby prepare a simple electrode which may be utilized to conduct electrochemical determinations either amperometrically or potentiometrically. Accurate determinations may be achieved in either operational mode. The present invention utilizes an electrode system which an enzyme material is covalently bonded to a treated substrate surface, with the electrode being stable, rugged, and useful for bio-determinations. The substrate surface is oxidized iridium to which a silanized film is applied, and therafter a glucose oxidase layer is covalently bonded to the treated substrate surface. A protective coverlay in the form of a silicone rubber film is preferably applied to the covalently bonded enzyme material, with such films accommodating the transport of glucose and oxygen for proper and accurate quantitative determinations.